The PARP enzyme occurring in the eukaryotic nucleus is a DNA-binding protein, having a serious role in the genomical repair mechanism.1,2 The PARP enzyme is activated directly by genotoxic agents (alkylating agents, reactive oxygen radicals, ionising radiation) or indirectly by DNA stand break occuring after the enzymatic excision of a mismatched DNA base. PARP catalyses the biochemical transformation of nicotinamide adenine dinucleotide (NAD) to poly(ADP-ribose) and nicotinamide, hence the latter is one of the weak feedback inhibiting agents of the enzyme. Although PARP plays an important role in the genomical repair, its significant activation entails extensive ADP-ribosylation and the depletion of NAD depots leading to the decrease of the ATP-level due to resynthesising NAD, and finally, in the lack of ATP and NAD it causes failure in the mitochondrial function and ultimately cell death.
The structural formulas of the first PARP inhibitors showed homology to nicotinamide and benzamide analogues.3 Recent research was aimed at the synthesis of more effective and more selective PARP inhibitors fitted to the crystal structure of PARP's catalytic domain, leading to the discovery of polycyclic amides and lactams.4,5 Presently, the most effective compound is 8-hydroxy-2-methyl-quinazoline-4(3H)-one [NU-1025, see formula (A), IC50=400 nM].6,7 Later, new tricyclic inhibitors were prepared starting from this compound.
The present inventors have already synthesised a promising antiarrhythmic 4-quinazolinone derivative named H-2641, see formula (B)8. After this, its PARP inhibiting activity could be studied and compared to the same of basic quinazolinone compounds of formulae (1)-(3). We note that, according to earlier observations, substitution at position 3 of the quinazolinone ring increased the IC50 value of the compounds, so further investigations in this direction did not seem to be promising.6 
The elaboration of the present invention was aimed at the preparation of new compounds containing the basic quinazoline-4(3H) ring bearing such sidechains in positions 2 or 3 that have an advantageous effect on the pharmacological properties of the molecule primarily by increasing their effect against oxidative stress due to the free radical trapping ability of the sidechains.
The effectiveness against oxidative stress can be an advantageous feature of the PARP inhibitors, because this way they can provide an increased protection against cell destruction caused by antiviral11 and antitumour drugs. The therapeutic application of antiviral and antitumour compounds unavoidably leads to the release of reactive oxygen free radicals. The in stau nascendi capture of these radicals can moderate the side effects of these drugs more than presently used PARP inhibitors could do.